FDA label d86229fa-7043-4069-9f64-bfd4c2f426d2

5 WARNINGS AND PRECAUTIONS • Serious, including fatal, hypersensitivity (anaphylactic) reactions. Discontinue TIMENTIN and institute appropriate therapy. ( 5.1 ) • Clostridium difficile associated diarrhea (CDAD). If diarrhea occurs, evaluate patients for CDAD. ( 5.2 ) • Convulsions may occur when the recommended dose of TIMENTIN is exceeded, especially in the presence of impaired renal function. Institute supportive measures. ( 5.3 ) 5.1 Anaphylactic Reactions Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. Before initiating therapy with TIMENTIN, inquire about previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, discontinue TIMENTIN and institute appropriate therapy. 5.2 Clostridium difficile Associated Diarrhea Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including TIMENTIN, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated. 5.3 Convulsions Patients may experience convulsions when the dose of TIMENTIN exceeds the recommended dose, especially in the presence of impaired renal function [see Adverse Reactions (6.2), Overdosage (10)] . 5.4 Risk of Bleeding Some patients receiving β-lactam antibacterials have experienced bleeding associated with abnormalities in coagulation tests. These adverse reactions are more likely to occur in patients with renal impairment. If bleeding manifestations appear, treatment with TIMENTIN should be discontinued and appropriate therapy instituted. 5.5 Potential for Microbial Overgrowth or Bacterial Resistance The possibility of superinfections with fungal or bacterial pathogens should be considered during therapy. If superinfections occur, appropriate measures should be taken. 5.6 Development of Drug-Resistant Bacteria Prescribing TIMENTIN in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug‑resistant bacteria. 5.7 Interference with Laboratory Tests High urine concentrations of ticarcillin may produce false-positive protein reactions (pseudoproteinuria) [see Drug Interactions (7.4)] . Clavulanic acid may cause a nonspecific binding of IgG and albumin by red cell membranes, leading to a false-positive Coombs test [see Drug Interactions (7.4)] . 5.8 Electrolyte Imbalance Hypokalemia has been reported during treatment with TIMENTIN. Serum potassium should be monitored in patients with fluid and electrolyte imbalance and in patients receiving prolonged therapy. The theoretical sodium content is 4.51 mEq (103.6 mg) per gram of TIMENTIN. This should be considered when treating patients requiring restricted salt intake.

6 ADVERSE REACTIONS The following are discussed in more detail in other sections of the labeling: • Anaphylactic Reactions [see Warnings and Precautions (5.1)] • Clostridium difficile Associated Diarrhea [see Warnings and Precautions (5.2)] Most common adverse reactions (≥1%) are rash, nausea, diarrhea, and phlebitis at injection site. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reactions occurring in ≥1% of 867 patients receiving TIMENTIN 3.1 grams in clinical studies included rash, nausea, diarrhea, and phlebitis at the injection site. The most common laboratory abnormalities (≥3%) were elevations in eosinophils, serum aspartate aminotransferase (AST), and serum alanine aminotransferase (ALT). Available safety data for pediatric patients treated with TIMENTIN demonstrate a similar adverse event profile to that observed in adult patients. 6.2 Postmarketing Experience In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postmarketing use of TIMENTIN. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These adverse reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to TIMENTIN. Hypersensitivity Reactions: Skin rash, pruritus, urticaria, arthralgia, myalgia, drug fever, chills, chest discomfort, anaphylactic reactions, and bullous reactions (including erythema multiforme, toxic epidermal necrolysis, and Stevens‑Johnson syndrome). Central Nervous System: Headache, giddiness, neuromuscular hyperirritability, or convulsive seizures. Gastrointestinal Disturbances: Disturbances of taste and smell, stomatitis, flatulence, nausea, vomiting and diarrhea, epigastric pain, and pseudomembranous colitis have been reported. Onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment [see Warnings and Precautions (5.2)] . Hemic and Lymphatic Systems: Thrombocytopenia, leukopenia, neutropenia, eosinophilia, reduction of hemoglobin or hematocrit, and prolongation of prothrombin time and bleeding time. Abnormalities of Hepatic Function Tests: Elevation of AST, ALT, serum alkaline phosphatase, serum LDH, and serum bilirubin. There have been reports of transient hepatitis and cholestatic jaundice, as with some other penicillins and some cephalosporins. Renal and Urinary Effects: Hemorrhagic cystitis, elevation of serum creatinine and/or BUN, hypernatremia, reduction in serum potassium, and uric acid. Local Reactions: Pain, burning, swelling, and induration at the injection site and thrombophlebitis with intravenous administration.